6. PROJECT SUMMARY/ABSTRACT This is a time of great excitement in the field of bone biology. In the past several years, we have gained great insight into how bone models and remodels, and this information has been applied to the treatment of osteoporosis and related skeletal disorders. Such knowledge has extended itself into areas that just a few years ago would have been incomprehensible. For example, the family of bone cells themselves, the osteoblast and the osteoclast, formerly thought to work in concert within the bone remodeling unit, now have been joined by the osteocyte, a cell newly recognized to play a pivotal role in signaling these cells and other systems. Products of these bone cells, also newly recognized, are identifying processes and mechanisms that extend to the very heart of molecular control mechanisms. This new knowledge has spanned a wide spectrum of disciplines that include cell and molecular biology, genetics, epidemiology, engineering, biomechanics, imaging, material sciences, immunology, and integrative organ physiology. Along with traditional areas that have housed the discipline, such as endocrinology and rheumatology, the field is now enriched with cross fertilization from these other areas, leading to new ideas and new knowledge. It is appropriate at this time, therefore, to hold a meeting in which these advances can be considered and in which experts in these various areas can gather together. The idea is to generate even more exciting ideas and therapeutic approaches to osteoporosis, which is a major cause of disability in our aging population. We believe it is important at this time to bring together clinical, basic and translational investigators to discuss these new advances with a view that will have therapeutic relevance. The proposed meeting will serve as an important step towards translating new knowledge into new therapeutic concepts. In addition, this meeting will identify key questions for future research. The American Society for Bone and Mineral Research is the premier society for the study and advancement of basic and clinical research in disorders relating to the skeleton. The considerations described above make it very clear that this is the time for senior thought leaders, mid-career investigators and young investigators to gather together in concert with NIH Institutes' staff. Information derived from the exchanges at such a meeting will serve to provide the NIH with novel ideas about programs worthy of support in future years and lead to a vibrant exchange of ideas and a definition of vital pathways for future advances in research and treatment. 7. PROJECT NARRATIVE Over the last several years, scientists from many different disciplines have contributed to an astonishingly fast improvement in our knowledge of bone modeling and bone remodeling. We understand, in ways never dreamed of several decades ago, how bone achieves its size and shape; how it adapts to changes in mechanical forces; how it senses the need to renew itself by breaking down old bone and replacing it with new bone within the multi-cellular bone remodeling unit; what cells, molecules and signaling pathways are involved in bone remodeling. This knowledge has been translated rapidly into greater understanding of the pathophysiology of bone loss, underlying genetic factors and elucidation of disease mechanisms. The delivery of this knowledge to the clinical arena has been nothing short of spectacular with therapeutics that are transforming how we think of a disease like osteoporosis, that not too long ago was viewed as an inevitable consequence of aging. Now, we have drugs that can prevent bone loss, can restore bone mass, can stimulate bone growth, can improve microarchitecture and can achieve the ultimate end point, the reduction of fracture risk. But, we recognize, at the same time, the need to understand more completely the skeleton in its complexity so as to make even greater strides in our attempt to literally cure this disease. The purpose of this meeting is to bring together experts from these interdisciplinary fields so as to define the direction of the future.